Striatal Neurons Expressing D₁ and D₂ Receptors are Morphologically Distinct and Differently Affected by Dopamine...

The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D₁ or D₂ dopamine receptor. Consequences on MSNs expressing both receptors (D₁/D₂ MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D₁/D₂ MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D₁/D₂ MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D₁ and D₂ MSNs, D₁/D₂ MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D₁/D₂ MSNs, but also of D₁ and D₂ MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D₁ and D₂ MSNs, the extent of dendritic arborization of D₁/D₂ MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D₁/D₂ MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson's disease.